It is known that the human genome contains about 10.sup.7 to 3.times.10.sup.7 polymorphic loci. Studies on human genetic variation have been substantially enhanced by the exploitation of restriction fragment length polymorphisms (RFLPs).
Several hundred probes detecting RFLPs have been characterized; most probes stem from the systematic searches of arbitrarily cloned DNA segments or from chromosome-specific libraries.
Generally, these human genetic markers detect single base exchanges of single copy sequences (Botstein et al., 1980). Yet, these several hundred probes are still not sufficient to allow for the identification of sufficient RFLPs which cover the human genome in short genetic intervals (about 10 cM). The human genome, however, contains unique repetitive DNA. Tandemly organized simple repetitive DNA which is interspersed frequently in the genome also shows base sequence polymorphisms. These RFLPs probably arise from unequal exchanges altering the number of tandem repeats in a given DNA fragment. Since numerous variants exist, many alleles can be defined. Because of the numbers and frequencies of their alleles, regions of interspersed simple repetitive DNA are regarded as the most informative genetic markers (White 1985). Taking advantage of certain interspersed repetitive DNAs, the so-called mini-satellites, Jeffreys and co-workers (1985 a, b, c) developed the principle of "DNA fingerprinting": cloned probes based on a core of tandemly repeated sequences that can detect many highly variable loci simultaneously and hence provide highly individual-specific hybridization patterns.
Another family of simple repeats, the GA A sequences, has originally been identified and isolated from female-specific snake satellite DNA (Epplen et al., 1982a). Subsequently, it was found that these Simple Quadruplet Repeats (sqr) are conserved throughout: the eukaryotes. In the human and the murine genomes the sqr are interspersed throughout the entire chromosomal complement (Epplen et al.. 1982b; Schafer et al., 1986a). These properties qualify the sqr as candidates for RFLP studies.